IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) e-ISSN: 2279-0853, p-ISSN: 2279-0861.Volume 13, Issue 3 Ver. IV. (Mar. 2014), PP 103-110 www.iosrjournals.org www.iosrjournals.org 103 | Page Insights into Common Microdeletion Syndromes Sathiya Maran 1 , Mehboob Alam Pasha 2 and Thirumulu Ponnuraj Kannan 1,3 1 Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia 16150 Kubang Kerian, Kelantan, Malaysia 2 Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia 16150 Kubang Kerian, Kelantan, Malaysia 3 School of Dental Sciences, Universiti Sains Malaysia 16150 Kubang Kerian, Kelantan, Malaysia Abstract : Microdeletion syndromes are due to submicroscopic chromosomal deletions and display a complex clinical and behavioral phenotype. This occurs because of an imbalance of normal dosage of genes that are present in that segment of chromosome. Many clinical characteristics of the well-known microdeletion syndromes are very specific and have been well defined. It is not always possible to detect these microdeletions by using the conventional or high resolution karyotyping. This necessitates the application of molecular cytogenetic techniques and the recent widespread usage and an in-depth knowledge of methods such as G-band karyotyping, multiples ligation-dependent probe amplification (MLPA), quantitative fluorescent PCR (QF- PCR), sequencing and microarray-based comparative genomic hybridization (array CGH) had further led to identification of new microdeletions and sound description of identification of new microdeletion syndromes. This review appraises the common microdeletion syndromes focusing on the incidence rate, clinical manifestations and the mechanism involved therein. Keywords: Clinical Features, Detection methods, Incidence rate, Microdeletion Syndromes I. Introduction Microdeletion syndromes are defined as a group of clinically recognizable disorders which are characterized by a small (<5Mb) deletion of a chromosomal segment spanning multiple disease genes, each potentially contributing to the phenotype independently [1]. Alongside, the recent explosion in the implementation of genome-wide microarray technology to discover rare, pathogenic genomic rearrangements in a variety of diseases has led to the discovery of numerous microdeletion syndromes [2]. These microdeletions are associated with extensive phenotypic heterogeneity and incomplete penetrance. The recurrent microdeletion had been reported to underpin diverse phenotypes, including intellectual disability, autism, epilepsy and neuropsychiatric disorders [2]. The Contiguous Gene syndromes in 1986 defined by Schmickel was the first to give rise to the ‘microdeletion syndromes’ which involved the deletion of a contiguous stretch of DNA, including multiple genes, on a chromosome [3].These syndromes are clinically recognized with distinct physical, behavioural, and mental characteristics and often involve some individual features that can be inherited in a Mendelian fashion [3]. The common microdeletion syndromes that have been reported till date are Smith-Magenis Syndrome, Miller-Dieker Syndrome, Prader-Willi Syndrome, Angelman Syndrome, Velocardiofacial Syndrome and DiGeorge Syndrome and Williams Syndrome [3] , which has been summarized in Table 1. II. Microdeletion Syndromes 1.1 Smith-Magenis Syndrome Smith-Magenis syndrome (SMS) is caused by the microdeletion at 17p11.2 and has been reported with an incidence rate of 1 in 25,000 births [3]. Clinical manifestations of SMS are craniofacial and skeletal anomalies, neurobehavioral abnormalities such as sleep disturbance and seizures, ophthalmic anomalies, otolaryngologic anomalies, cardiac and renal anomalies [4]. The major phenotypes of SMS are distinctive craniofacial features including brachycephaly, a broad face, frontal bossing, synophrys, hypertelorism, upslanting eyes, midface hypoplasia with a depressed nasal bridge, a tented upper lip, prognathism, and low-set or abnormally shaped ears [5, 6]. SMS is associated with deletion and mutation on the RAI1 gene located at chromosome 17p11.2 [7] Majority of the patients (75-90%) harbour a ∼4 Mb deletion [8-10]. Meanwhile, patients with smaller deletions show deletion of about 20 genes [11]. The SMS phenotype is variable even in patients with deletions of the same size [9]. Although the exact mechanism of SMS has yet to be elucidated, abnormalities in the expression of SREBF1, MYO15, COPS3, PMP22 and other genes may also contribute to the specific clinical features, elevated cholesterol levels, peripheral neuropathy, hearing loss and abnormal sleep patterns [12-16]. The